Diabetologia https://doi.org/10.1007/s00125-017-4522-x
ARTICLE
Social deprivation modifies the association between incident foot ulceration and mortality in type 1 and type 2 diabetes: a longitudinal study of a primary-care cohort Simon G. Anderson 1 & Haika Shoo 2 & Sushant Saluja 1 & Christian D. Anderson 3 & Adnan Khan 4 & Mark Livingston 5 & Edward B. Jude 6 & Mark Lunt 7 & George Dunn 8 & Adrian H. Heald 9,10 Received: 22 June 2017 / Accepted: 25 September 2017 # The Author(s) 2017. This article is an open access publication
Abstract Aims/hypothesis The aim of this study was to determine whether social deprivation in the presence of diabetes is an independent predictor of developing a foot ulcer and separately of mortality. Methods This was a primary-care-based retrospective analysis of 13,955 adults with type 1 (n = 1370) or type 2 (n = 12,585) diabetes after a median follow-up of 10.5 years. Demographic characteristics, indices of social deprivation and clinical variables were assessed at baseline. The primary outcomes were new foot ulceration (in those without a previous history of foot ulcers) and all-cause mortality. Cox proportional hazard models were used to describe the associations among foot ulceration, social deprivation and mortality. Results The mean age of the population was 69.4 (range: 16–89) years. The incidence of foot ulceration was greater in individuals with type 2 (8.6%) compared with type 1 diabetes (4.8%). Occurrence was similar by sex, but increased with age and deprivation index. Individuals in the highest quintile of deprivation were 77% more likely to develop a foot ulcer compared with those in the lowest quintile (OR 1.77 [95% CI 1.45, 2.14], p < 0.0001). Overall, 2946 (21.1%) deaths were recorded. Compared with individuals without a foot ulcer, the development of a foot ulcer was associated with a higher age- and sex-adjusted mortality rate (25.9% vs 14.0%), and a 72% (HR 1.72 [95% CI 1.56, 1.90], p < 0.001) increased risk of mortality in those with type 2 diabetes. Risk of death increased by 14% per quintile of deprivation in a univariable analysis (HR 1.14 [95% CI 1.10, 1.17]). In multivariable Cox regression analyses, there was a 48% increased risk of mortality in individuals with a foot ulcer (HR 1.48 [95% CI 1.33, 1.66]) independent of the Townsend index score (HR 1.13 [95% CI 1.10, 1.17], per quintile), baseline age, sex, diabetes type, smoking status, hypertension, statin use, β-blocker use, metformin use, HbA1c levels and insulin use.
Simon G. Anderson and Haika Shoo contributed equally to this study. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-017-4522-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users. * Adrian H. Heald
[email protected] 1
Division of Cardiovascular Sciences, Faculty of Biology, Medicine, and Health, Core Technology Facility, The University of Manchester, Manchester, UK
2
Diabetes and Endocrine Department, East Cheshire NHS Trust, Macclesfield, UK
3
School of Medicine, University of Liverpool, Liverpool, UK
4
Department of Endocrinology and Diabetes, Leighton Hospital, Crewe, UK
5
Department of Blood Sciences, Walsall Manor Hospital, Walsall, UK
6
Department of Diabetes and Endocrinology, Tameside Hospital NHS Foundation Trust, Ashton-under-Lyme, UK
7
Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, School of Biological Sciences and Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
8
Department of Podiatry, East Cheshire NHS Trust, Macclesfield, UK
9
Salford Royal NHS Foundation Trust, Diabetes and Endocrinology, Stott Lane, Salford, UK
10
School of Medical Sciences, Faculty of Biology, Medicine, and Health, and Manchester Academic Health Science Centre (MAHSC), The University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK
Diabetologia
Conclusions/interpretation This study confirms the high mortality rate in individuals with diabetes-related foot ulcers. In addition, socioeconomic disadvantage was found to be an independent effect modifier, contributing to an increased burden of mortality in people with diabetes who develop foot ulceration. In light of this, and as diabetes service configurations are orientated for the next 5–10 years, modelling of foot ulceration risk needs to take socioeconomic disadvantage into account. Keywords Deprivation index . Diabetes . Foot ulcer . Mortality
Abbreviation GP General practitioner
Introduction Foot ulceration is the most common complication in diabetes, with a lifetime risk of 25% [1]. The condition portends significant excess morbidity and mortality in individuals with diabetes, who are already facing reduced life expectancy and an unfavourable prognosis [1–5]. Established aetiological risk factors for foot ulceration in diabetes are suboptimally controlled diabetes, peripheral neuropathy, peripheral vascular disease, foot deformity and previous foot ulceration [1, 6]. Diabetic foot ulceration is a global public health issue, with a prevalence of 13.0% in North America and 5.1% in Europe [7]. The incidence in Europe is around 2% per year [8]. Costs of care are double those seen in individuals without ulceration [9], with the total cost associated with treatment being as high as €10 billion per year in Europe [8]. The incidence of foot ulcers is 2.2% per annum in the UK, and an average of 6000 people with diabetes each year undergo amputation [10, 11]. The financial burden is significant in terms of both healthcare costs and long-term consequences. The annual UK National Health Service expenditure on diabetes foot-related care in 2010–2011 was estimated to be £580 million (US$748 million), representing around 0.6% of total expenditure [12]. Within 5 years (2014–2015), after accounting for inflation, estimates rose to between £972 million and £1.13 billion (US$1.29–1.50 billion), with two-thirds of these costs spent on care for foot ulceration in primary, community and outpatient settings [13]. Consequently, better precision in understanding the risk calculus in relation to the development of diabetic foot ulcers and the likelihood of death in such individuals will result in reduced health service costs and potential cost savings in the longer term. Previous epidemiological studies have shown a strong association between socioeconomic disadvantage and the prevalence of diabetes [14, 15]. In the general population, mortality is greater in those from a more disadvantaged socioeconomic situation, principally as a result of cardiovascular disease [16]. In the presence of diabetes, however, mortality rates are significantly greater in individuals who live in relatively deprived areas [17]. Furthermore, depression has been found to be associated with a 2.3-fold increase in mortality vs no
depression in individuals with diabetes [18]. Psychological factors other than coded diagnoses are difficult to quantify in epidemiological studies, but are clearly important. The literature on the association between social deprivation and foot ulceration in individuals with diabetes is inconsistent. Two UK studies have shown no association between socioeconomic disadvantage and foot ulceration [19, 20]. Conversely, one Scottish study considered healthcare accessibility as well as socioeconomic disadvantage in the population and demonstrated evidence of increased foot ulceration in the more disadvantaged areas within Scotland [21]. The Eurodiale study has reported that low health-related quality of life is predictive of major amputation and mortality [22]. Few studies have looked at social disadvantage as an independent risk factor in diabetes foot ulceration and as a risk factor for mortality in those with a foot ulcer. The first aim of this study was to determine whether social deprivation is an independent predictor of foot ulceration in people with diabetes in a population with significantly varying levels of social disadvantage. Second, we tested the hypothesis that foot ulceration and level of social disadvantage independently predict all-cause mortality in individuals with type 2 diabetes.
Methods We examined pseudo-anonymised electronic health records from a retrospective cohort of all men and women aged 16– 89 years attending 42 general practices in central and eastern Cheshire, UK. The area is a mixed urban and rural environment with a wide range of socioeconomic situations, from significantly disadvantaged urban areas to highly affluent suburbs. The total population of the geographical area studied was 475,000, and the prevalence of significant social disadvantage (based on multiple measures) was 23%. Individuals were eligible for inclusion if they had a diagnosis of diabetes prior to cohort entry at 1 January 2004 to allow long-term follow-up and no prior history of foot ulceration. A data search was performed through the centralised data facility afforded by Egton Medical Information Systems (EMIS), a commercial organisation that provides health information for nearly all family practices in Cheshire. Permission for this study was sought from and granted by the local information governance and ethics committees. Informed consent was not required as all data were anonymised.
Diabetologia
Exposure For the main search, we included all individuals using the relevant READ codes for type 1 and type 2 diabetes. READ codes are used in a hierarchical clinical coding system of more than 80,000 terms that is used in general practice across the UK [23]. The READ codes used in this study are available from the Clinical Codes repository (www. clinicalcodes.org) [24]. We examined the electronic health records of the included individuals to determine the presence of foot ulcers occurring after 1 January 2004 using the relevant READ codes. Outcomes For all individuals, the outcomes were foot ulceration and all-cause mortality during the study period. Currently, the reporting of deaths within UK primary care is well established, and if an individual dies in secondary or tertiary care then a general practitioner (GP) must be notified of the death. The date of death was ascertained from GP records. We controlled for survival bias by following all participants from the same point in time: a landmark of 6 months post 1 January 2004. Follow-up was censored at death, the date an individual left the practice or the final data collection for the practice (30 June 2015), whichever occurred first. Variables Data on potential confounders, including age on the date of inclusion, sex, diabetes type and duration, hypertension (defined as BP >140/90 mmHg on two or more readings, as per READ codes), diabetes treatment (oral medication, glucagon-like peptide 1 or insulin), metabolic control (through HbA1c) and smoking habits (unreported status, current/exsmoker and non-smoker), were recorded, as was the prescribing of statins and antihypertensive agents. The Townsend index of deprivation (categorised by quintiles) was determined in our study population [25]. This information is available in GP records linking the postcode of the individual with UK census data. The Townsend index was devised to provide a material measure of deprivation and socioeconomic disadvantage in a population, and derives from census variables taken originally from the 1991 UK census, with numerically higher values suggesting greater socioeconomic deprivation. The four variables that comprise the Townsend index are as follows: (1) unemployment as a percentage of those aged 16 years and over who are economically active; (2) non-car ownership as a percentage of all households; (3) non-home ownership as a percentage of all households; and (4) household overcrowding. All four variables are standardised using a z score and then summed to obtain a single value. Positive values of the Townsend index are associated with geographic areas with high deprivation, while indices with negative values relate to relative affluence. While the central and eastern Cheshire region is predominantly of white European ethnicity, records pertaining to ethnicity were only available for a small proportion (70 years old) and in individuals with type 2 compared with type 1 diabetes (8.6% [n = 1081] vs 4.8% [n = 66], χ2 = 23.3; p < 0.001). In the full cohort, stratified by sex, the occurrence of foot ulceration rate was similar (508/6011 [8.4%]) in women and men (639/7944, [8.0%]). However, amongst those who developed foot ulceration [n = 1147], a greater proportion were male (55.7% vs 44.3%; male versus female, p = 0.0001; Tables 1 and 2). At baseline, greater proportions of individuals with foot ulceration had hypertension, cerebrovascular disease, peripheral vascular disease and a previous myocardial infarction (all p < 0.01, Table 1). Mean systolic and diastolic blood pressure and levels of creatinine and LDL-cholesterol were greater in the presence of foot ulceration in individuals with type 2 diabetes (Table 2). No differences were observed in type 1 diabetes for these covariates. Social deprivation and foot ulceration rates For those with foot ulceration, there were between one and 15 recorded episodes per person over the follow-up period, with an incidence rate of 0.9% per year. The unadjusted incidence rate ratio for a foot ulcer was 39% lower for individuals with type 1 vs type 2 diabetes (incidence rate ratio 0.61 [95% CI 0.47, 0.77], p < 0.001). Individuals in the fifth quintile of deprivation were 77% more likely to develop a foot ulcer over the follow-up period compared with those in the first quintile (OR 1.77 [95% CI 1.45, 2.14], p < 0.0001; Fig. 1).
2 diabetes, there was an almost doubling of the risk of mortality in unadjusted shared frailty Cox regression analyses clustered by practice (HR 1.93 [95% CI 1.74–2.15], p < 0.0001; Fig. 3), with some attenuation of the size of the effect after age- and sex-adjustment (HR 1.71 [95% CI 1.54, 1.90], p < 0.001). In similar age- and sex-adjusted models including only those with no prior/current history of foot ulceration, increased deprivation (per quintile) was associated with increased mortality in those with type 2 diabetes (HR 1.13 [95% CI 1.09, 1.16], p < 0.0001), but not in those with type 1 diabetes (HR 1.05 [95% CI 0.86, 1.27], p = 0.063; ESM Table 1). Social deprivation and death in individuals with foot ulcer Death rates increased per quintile of deprivation in individuals with diabetes and foot ulceration (absolute difference between the first and fifth quintile 19.54 deaths per 1000 person-years; Fig. 4). Risk of death increased by 14% per quintile of deprivation in a univariable analysis (HR 1.14 [95% CI 1.10, 1.17%]) for all individuals. For individuals with type 2 diabetes, the risk of mortality in those who developed foot ulceration increased by 11% per quintile of deprivation (HR 1.11% [95% CI 1.08%, 1.14%], p < 0.0001). The association of deprivation with mortality in type 1 diabetes was not significant (HR 1.14 [95% CI 0.96, 1.36%], p = 0.136). In shared frailty, multivariable Cox regression analyses clustered by practice, foot ulceration (HR 1.48 [95% CI 1.33, 1.66], p < 0.0001) independently predicted long-term mortality after adjustment for age, sex, diabetes type, Townsend index score (HR 1.13 [95% CI 1.10, 1.17], per quintile), smoking status, hypertension, statin treatment, βblocker treatment, metformin use, HbA 1c level (per 10 mmol/mol) and insulin use (Fig. 5). There was no interaction between foot ulceration and the Townsend index score for deprivation (χ2 = 1.49; p for interaction = 0.475).
Discussion Foot ulceration rates and mortality Over a median follow-up period of 10.5 years there were 2946 (21.1%) deaths. Ageand sex-adjusted mortality rates in the group with foot ulcers were approximately twice those in the group without a foot ulcer (25.9% vs 14.0%; 41.6 vs 20.5 deaths per 1000 personyears, respectively). In the presence of type 2 and type 1 diabetes, the mortality rates for individuals with foot ulceration were 43.3 (95% CI 39.3, 47.7) and 16.9 (95% CI 9.3, 30.6) per 1000 person-years, respectively. Foot ulceration was associated with an increased risk of mortality in individuals with type 1 diabetes in unadjusted shared frailty Cox proportional hazard models clustered by practice (HR 4.45 [95% CI 2.29– 8.64]; Fig. 2), but not after adjustment for age and sex (HR 1.55 [95% CI 0.79, 3.07], p = 0.20). For individuals with type
In this retrospective cohort followed for 10.5 years, individuals with diabetes-related foot ulceration had a higher risk of all-cause mortality than those without a history of foot ulceration. Specifically, after multivariable adjustment, a 48% increased risk of mortality was observed in those who developed a foot ulcer. We also found that social deprivation is an independent predictor of mortality, with the risk of death increasing by 13% per quintile of deprivation (HR 1.13 [95% CI 1.10, 1.17]) independent of baseline age, sex, diabetes type, smoking status, hypertension, statin, β-blocker or metformin use, HbA1c level and insulin use. Individuals in the highest quintile of deprivation were 77% more likely to develop a foot ulcer compared with those in the lowest quintile.
Diabetologia Table 1 Baseline characteristics of all individuals by the presence or absence of foot ulceration
Variable
Total population Foot ulcera (n=1147)
No foot ulcer (n=12,808)
p valueb
Age, years
74.2 (73.3, 74.2)
69.0 (68.8, 69.3)
